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辐射诱导的氧化应激:I. 对小鼠艾氏实体瘤的研究。

Radiation induced oxidative stress: I. Studies in Ehrlich solid tumor in mice.

作者信息

Agrawal A, Choudhary D, Upreti M, Rath P C, Kale R K

机构信息

School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.

出版信息

Mol Cell Biochem. 2001 Jul;223(1-2):71-80. doi: 10.1023/a:1017900810837.

Abstract

Understanding the response of tumors to ionizing radiation might potentially lead to improvement in tumor control and patient morbidity. Since the antioxidant status is likely to be linked to radioresponse, its modulation needs to be examined. Therefore, Swiss albino male mice (7-8 weeks old) with Ehrlich solid tumors were irradiated with different doses of gamma rays (0-9 Gy) at a dose rate of 0.0153 Gy/s; and enzymes involved in antioxidant functions were determined in the tumors. Radiation effects in terms of oxidative damage, LDH, nitric oxide and DNA fragmentation were also examined. In tumors, the specific activity of SOD was increased with dose but declined 6 Gy onwards. GST, DTD and GSH showed an almost progressive increase. These enhanced activities might have resulted from the increased protein expression. This possibility was supported by the Western Blot analysis for GST protein. These changes might be closely linked to the radiation-induced oxidative stress as reflected by the enhanced levels of peroxidative damage, DNA fragmentation, LDH activity and nitric oxide levels. These findings may have relevance to radiation therapy of cancer as the elevated antioxidant status of irradiated tumors is likely to limit the effectiveness of radiation dose and adversely affect the therapeutic gain.

摘要

了解肿瘤对电离辐射的反应可能会潜在地改善肿瘤控制和患者的发病率。由于抗氧化状态可能与放射反应相关,因此需要研究其调节作用。因此,对患有艾氏实体瘤的瑞士白化雄性小鼠(7 - 8周龄)以0.0153 Gy/s的剂量率用不同剂量的γ射线(0 - 9 Gy)进行照射;并测定肿瘤中参与抗氧化功能的酶。还检测了氧化损伤、乳酸脱氢酶(LDH)一氧化氮和DNA片段化方面的辐射效应。在肿瘤中,超氧化物歧化酶(SOD)的比活性随剂量增加而升高,但在6 Gy及以上剂量时下降。谷胱甘肽S - 转移酶(GST)、二硫代二硝基苯甲酸还原酶(DTD)和谷胱甘肽(GSH)呈现几乎逐渐增加的趋势。这些活性的增强可能是由于蛋白质表达增加所致。谷胱甘肽S - 转移酶蛋白的蛋白质印迹分析支持了这种可能性。这些变化可能与辐射诱导的氧化应激密切相关,这可通过过氧化损伤、DNA片段化、乳酸脱氢酶活性和一氧化氮水平的升高反映出来。这些发现可能与癌症放射治疗相关,因为受照射肿瘤升高的抗氧化状态可能会限制辐射剂量的有效性,并对治疗增益产生不利影响。

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